The sequential cellular changes that occur in the livers of Fischer rats exposed to the hepatocarcinogen N-2-fluorenylacetamine will be analyzed. Recently developed systems employing cyclic feedings as well as feeding carcinogen in choline deficient diets will be used in conjunction with cellular labeling techniques to carry out lineage studies on newly appearing cell types. A series of 18 related experiments is presented. These are designed to answer the following questions: 1) Why do animals die from the acute effects of carcinogen exposure? 2) What is the effect of sex and age on hepatocarcinogenesis? 3) What is the effect of feeding carcinogen in a choline deficient diet? 4) What are some of the factors modifying the toxic effects of carcinogen fed in a choline deficient diet? 5) What is the origin of the new cell types which appear? 6) What is the fate of the newly appearing cell types? 7) What is the effect of carcinogen exposure on molecular mechanisms controlling alphafetoprotein synthesis? In particular, the role of different liver cell types as precursors of cancer cells should be clarified. Although limited to a detailed study of one carcinogen in a single strain of rat the results should be applicable to other systems of chemical carcinogenesis.